New surgical approaches to Parkinson's disease (PD) have been developed in recent years. Behavioral recovery following caudate cavitation and/or cell implants in the CNS has brought the focus on the therapeutic potential of neurotrophic factors and the neurite outgrowth and glial proliferation they promote. On the other hand, electrophysiologic studies have brought attention to the hyperactivity of the globus pallidum (Gpi) neurons as a major effect of the dysregulation in this disease. Localized lesions of GPi as a way to restore physiological balance are now being used in human patients. In our laboratory, we have developed a method of direct drug delivery to the white or grey matter of the CNS, which allows us to study both approaches. We are currently infusing mid size proteins into the putamen of rhesus monkeys as a feasibility study for infusion of BDNF and/or GDNF. At the same time, we have also assessed the potential of convection-enhanced infusion of excitotoxins as a tool for superselective lesioning of the GPi. Using this technique, we can selectively ablate the neurons of Gpi, reversing parkinsonism in MPTP-lesioned monkeys, without the risk of any white matter damage to the surrounding areas.